Abnormal Responses of Myeloid Progenitor Cells to GM-CSF (Granulocyte-Macrophage-Colony-Stimulating Factor) in Human Cyclic Neutropenia
Abstract
Granulocyte-macrophage progenitors (CFU-GM) from four patients with childhood onset cyclic neutropenia demonstrated abnormal in vitro proliferative responses to purified, recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) when examined in detailed dose-response studies. Marrow aspirate specimens were obtained for these studies from cyclic neutropenia patients (both during neutropenic nadirs and during recovery phases of cycles), from leukemia patients in remission who had received myelosuppressive chemotherapy, and from healthy normal volunteers. Nucleated marrow cells were then isolated by density gradient centrifugation and cryopreserved to permit studies of CFU-GM from patients and controls. Maximum clonal growth of CFU-GM from normal subjects and from individuals recovering from drug-induced myelosuppression was elicited by 20 to 100 pmol/L rhGM-CSF, and the CSF concentrations that induced half-maximal responses. Maximum growth of CFU-GM from the cyclic neutropenia patients required > or = 1.0 nmol/liter rhGM-CSF and ED50's were > 30.0 pmol/liter. These abnormalities in the GM-CSF responsive growth of myeloid progenitors were independent of cycle time and were most apparent with the predominantly neutrophilic 7-d CFU-GM. These findings indicate that childhood onset cyclic neutropenia is associated with an underlying disturbance in the GM-CSF responsive growth of myeloid progenitors committed to neutrophilic differentiation. Reprints.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 1989
- Accession Number
- ADA212563
Entities
People
- August J. Salvado
- Daniel G. Wright
- Robert D. Knight
- Vincent F. Larussa